Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16-negative squamous cell carcinoma of the oropharynx

被引：28

作者：

Junor, E. ^{[1
]}

Kerr, G. ^{[1
]}

Oniscu, A. ^{[2
]}

Campbell, S. ^{[1
]}

Kouzeli, I. ^{[3
]}

Gourley, C. ^{[4
]}

Cuschieri, K. ^{[3
]}

机构：

[1] Western Gen Hosp, Edinburgh Canc Ctr, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Royal Infirm Edinburgh NHS Trust, Dept Pathol, Edinburgh EH16 4SA, Midlothian, Scotland

[3] Royal Infirm Edinburgh NHS Trust, Scottish HPV Reference Lab, Edinburgh EH16 4SA, Midlothian, Scotland

[4] Univ Edinburgh, Canc Res UK Ctr, Inst Genet & Mol Med, Edinburgh EH4 2XR, Midlothian, Scotland

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 02期

关键词：

HPV; P16; squamous cancer; oropharynx; HUMAN-PAPILLOMAVIRUS; FAVORABLE PROGNOSIS; NECK CANCERS; HEAD; SURVIVAL; EXPRESSION; DIAGNOSIS; PROFILES;

D O I：

10.1038/bjc.2011.542

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: To determine (a) the cause of an improvement in survival from oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b) whether this improvement was human papillomavirus (HPV) and p16 subtype-dependent. METHODS: Clinicopathological characteristics and outcome data for patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort-2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were performed from paraffin blocks. RESULTS: Cohort-1 and Cohort-2 contained 118 and 136 patients, respectively. Kaplan-Meier analysis revealed significantly improved survival in Cohort-2 (P<0.0001). Sub-classification according to HPV and p16 status revealed no improvement in survival in Class-I (HPV-ve/p16-ve; 47 patients) or Class-III (HPV+ve/p16+ve; 77 patients). However in Class-II (HPV+ve/p16-ve; 56 patients) an increase in 5-year cause-specific survival from 36% in Cohort-1 to 73% in Cohort-2 was detected (P=0.0001). Proportional hazards analysis of 217 patients treated radically demonstrated that significant variables were p16 (Po0.0001), N stage (P=0.0006) and cohort (P=0.0024). Removing cohort from the variables offered to the model showed that, whereas p16 (Po0.0001) and N stage (P=0.0016) remain significant, chemotherapy (P=0.0163) and T stage (P=0.0139) are now significant. This suggests that much of the cohort effect is due to the higher use of chemotherapy in the second cohort. CONCLUSION: These data suggest that HPV=ve/p16-ve patients constitute a separate subclass of OSCC who may particularly benefit from chemotherapy. They imply that p16 status cannot be considered a surrogate for HPV status, and those trials to de-escalate treatment in HPV+ve OSCC should take p16 status into account. British Journal of Cancer (2012) 106, 358-365. doi:10.1038/bjc.2011.542 www.bjcancer.com Published online 6 December 2011 (C) 2012 Cancer Research UK

引用

页码：358 / 365

页数：8

共 21 条

[1] Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer [J].

Ang, K. Kian ;

Harris, Jonathan ;

Wheeler, Richard ;

Weber, Randal ;

Rosenthal, David I. ;

Nguyen-Tan, Phuc Felix ;

Westra, William H. ;

Chung, Christine H. ;

Jordan, Richard C. ;

Lu, Charles ;

Kim, Harold ;

Axelrod, Rita ;

Silverman, C. Craig ;

Redmond, Kevin P. ;

Gillison, Maura L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (01) :24-35

[2] Moderate predictive value of demographic and behavioral characteristics for a diagnosis of HPV16-positive and HPV16-negative head and neck cancer [J].

D'Souza, Gypsyamber ;

Zhang, Hao H. ;

D'Souza, Warren D. ;

Meyer, Robert R. ;

Gillison, Maura L. .

ORAL ONCOLOGY, 2010, 46 (02) :100-104

[3] Mechanisms of genomic instability in human cancer:: Insights from studies with human papillomavirus oncoproteins [J].

Duensing, S ;

Münger, K .

INTERNATIONAL JOURNAL OF CANCER, 2004, 109 (02) :157-162

[4] Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial [J].

Fakhry, Carole ;

Westra, William H. ;

Cmelak, Sigui Li Anthony ;

Ridge, John A. ;

Pinto, Harlan ;

Forastiere, Arlene ;

Gillison, Maura L. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (04) :261-269

[5] Changing patterns of tonsillar squamous cell carcinoma in the United States [J].

Frisch, M ;

Hjalgrim, H ;

Jæger, AB ;

Biggar, RJ .

CANCER CAUSES & CONTROL, 2000, 11 (06) :489-495

[6] The Isolation of Nucleic Acids from Fixed, Paraffin-Embedded Tissues-Which Methods Are Useful When? [J].

Gilbert, M. Thomas P. ;

Haselkorn, Tamara ;

Bunce, Michael ;

Sanchez, Juan J. ;

Lucas, Sebastian B. ;

Jewell, Laurence D. ;

Van Marck, Eric ;

Worobey, Michael .

PLOS ONE, 2007, 2 (06)

[7] Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers [J].

Gillison, Maura L. ;

D'Souza, Gypsyamber ;

Westra, William ;

Sugar, Elizabeth ;

Xiao, Weihong ;

Begum, Shahnaz ;

Viscidi, Raphael .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2008, 100 (06) :407-420

[8]

Gillison ML, 2009, AM SOC CLIN ONCOLOGY, V27

[9] Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets [J].

Hong, Angela M. ;

Grulich, Andrew E. ;

Jones, Deanna ;

Lee, C. Soon ;

Garland, Suzanne M. ;

Dobbins, Timothy A. ;

Clark, Jonathan R. ;

Harnett, Gerald B. ;

Milross, Christopher G. ;

O'Brien, Christopher J. ;

Rose, Barbara R. .

VACCINE, 2010, 28 (19) :3269-3272

[10] Oropharyngeal cancer Fastest increasing cancer in Scotland, especially in men [J].

Junor, Elizabeth J. ;

Kerr, Gillian R. ;

Brewster, David H. .

BRITISH MEDICAL JOURNAL, 2010, 340

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